Lynn Farner, Paulina S. Scheuren, Kiomars Sharifi, Tim M. Emmenegger, Maryam Seif, Michèle Hubli, Martin Schubert, M.F. Bolliger, Rüdiger Rupp, Norbert Weidner, Rainer Abel, Doris Maier, Klaus Röhl, Michael Baumberger, Margret Hund‐Georgiadis, Marion Saur, Jesús Benito, Kerstin Rehahn, Mirko Aach, Andreas Badke, Jiri Kriz, Tim Killeen, Alan J. Thompson, Nikolaus Weiskopf, Martin E. Schwab, Armin Curt, Patrick Freund, the Nogo Inhibition in Spinal Cord Injury (NISCI) Study Group
NG101 is a recombinant antibody that neutralizes the nerve growth inhibitor Nogo-A, promoting neural repair and improving upper extremity motor function in spinal cord injury (SCI). This study evaluated spinal cord MRI biomarkers to detect treatment-related structural changes and enhance patient stratification using data from 106 participants with acute cervical SCI in the phase 2b NISCI trial. We assessed lesion volume, tissue bridges, and remote changes in cross-sectional cord area (CSA), and tract-specific myelin-sensitive magnetization transfer saturation (MTsat) over six months. Compared to placebo, NG101-treated participants exhibited faster lesion volume reduction and a slower decline of CSA and MTsat in the corticospinal tracts and dorsal columns. Crucially, multimodal stratification incorporating MRI and electrophysiological measures substantially enhanced the detection of clinical treatment effects. These findings suggest NG101 slows trauma-induced progressive macro- and microstructural degeneration or promotes fiber sprouting. Combining MRI with electrophysiology enables sensitive detection of treatment effects and efficient trial designs. ClinicalTrials.gov identifier: NCT03935321.